EP0935459A1 - Verfahren zur herstellung einer pharmazeutischen zusammensetzung mitveränderte wirkstoffsfreisetzung, enthaltend eine matrix - Google Patents
Verfahren zur herstellung einer pharmazeutischen zusammensetzung mitveränderte wirkstoffsfreisetzung, enthaltend eine matrixInfo
- Publication number
- EP0935459A1 EP0935459A1 EP97943017A EP97943017A EP0935459A1 EP 0935459 A1 EP0935459 A1 EP 0935459A1 EP 97943017 A EP97943017 A EP 97943017A EP 97943017 A EP97943017 A EP 97943017A EP 0935459 A1 EP0935459 A1 EP 0935459A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- manufacturing
- pharmaceutical composition
- grains
- modified release
- matrix agent
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1611—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2009—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5015—Organic compounds, e.g. fats, sugars
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
- A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
Definitions
- the invention relates to a method for manufacturing a pharmaceutical composition with modified release of active principle, comprising a matrix.
- “Pharmaceutical composition with modified release of active principle” means pharmaceutical compositions with accelerated, prolonged and delayed release of active principle.
- compositions with modified release of active principle comprising, on the one hand, uncoated granules constituting the dose of active principle immediately available and, on the other hand, coated granules ensuring the modified release of active principle.
- compositions comprising a matrix effect are also used.
- the invention relates more particularly to the method for manufacturing the latter.
- the active ingredient is dispersed or coated in a solid system, called a matrix.
- the active ingredient is released from the matrix by contact with biological fluids with said matrix. More precisely, the biological liquids migrate through the matrix and dissolve the active ingredients and these are released by diffusion through the matrix which, simultaneously, modulates the release flow.
- hydrophilic matrices hydrophilic matrices and hydrophobic matrices.
- the matrix consists of an insoluble hydrophilic polymer whose concentration is between 25% and more than 50% of the weight of the composition, therefore high.
- This polymer is chosen from cellulose esters, carboxyvinyl esters, or even acrylic or methacrylic esters.
- the matrix On contact with biological liquids, the matrix hydrates and swells, forming a very dense network of polymers through which diffuse the soluble active ingredients.
- these compositions contain numerous adjuvants, often expensive, at high concentrations, which considerably increases the cost of the composition.
- compositions are obtained by granulation and then compression of the mixture formed from the polymer, the active ingredients and the various adjuvants. These techniques often call for the use of organic solvents, which it is then essential to recover, to avoid their dispersion in the atmosphere. In addition, traces of toxic solvent may remain in the final product, which traces must necessarily be quantified.
- the matrix consists of a lipid matrix agent, of natural origin, for example beeswax, having a high innocuity, but the composition of which from one batch to another varies and whose stabilization over time remains unsatisfactory.
- compositions are generally obtained by granulation, wet or solvent, then compression, using high proportions of each of the constituents.
- the aim of the invention is therefore to propose a new process for the manufacture of a pharmaceutical composition with modified release of active principle with the aim of significantly reducing the number and the proportions of each of the constituents as well as the number of 'operations, thus making it possible to obtain a formulation that is simple to implement, and of low cost and reproducible.
- the invention provides a method of manufacturing a pharmaceutical composition with modified release of active principle, comprising at least one active principle, a lipid matrix agent consisting of an ester of at least one fatty acid and alcohol, and at least one adjuvant.
- This process is characterized in that:
- a powder consisting of at least one component selected from the group comprising the active principle and the adjuvant is mixed, in order to obtain individualized grains,
- the invention resides in the implementation of a specific process which makes it possible to reduce the number of adjuvants necessary for producing the composition, and therefore to end up with an extremely simple and low formula. cost.
- the process of the invention does not require an evaporation phase, nor a drying phase, since it does not require a wet or solvent granulation step, thus making it possible to be free from any risk. due to the presence of toxic residues in the final product. In addition, there is no longer any need to carry out the determination of traces of solvents, a very expensive analysis.
- the spray air pressure can be increased in order to promote the formation of a homogeneous film of lipid matrix agent around the grains.
- the spraying rate of the lipid matrix agent can be reduced simultaneously.
- an active principle release profile is obtained, that is to say a very low percentage of dissolution as a function of time, corresponding to a slow release of the active principle.
- the spray air pressure can be reduced in order to promote the agglomeration of the grains between them.
- the spraying rate of the lipid matrix agent can be increased simultaneously.
- the value of the spraying rate of the lipid matrix agent is two to four times higher when it is desired to promote the agglomeration of the grains between them than when we want to promote the formation of a homogeneous film around the grains.
- the value of the spraying air pressure is one to two times lower when it is desired to promote the agglomeration of the grains between them than when it is desired to promote the formation of a homogeneous film around the grains.
- the coating operation can be carried out continuously and automatically.
- the temperature of the mixture of liquefied matrix agent and atomizing air must be greater from 35 ° C. to 60 ° C. than the melting temperature of the lipid matrix agent.
- the temperature of the fluidizing air and that of the powder must be equal to the melting temperature of the lipid matrix agent, more or less 10 ° C.
- a fluidized air bed device or a turbine device is used.
- the spraying of the lipid matrix agent can be carried out by the technique called "AIR SPRAY", that is to say a liquid spraying under pressure in the presence of compressed air.
- a powder comprising the active principle and the adjuvant.
- the lipid matrix agent is sprayed onto the individualized grains obtained.
- the spraying air pressure and the spraying rate of lipid matrix agent are adjusted to a value which makes it possible to promote the formation of a homogeneous film of lipid matrix agent around the grains.
- the coated grains are subjected to a compression step.
- a powder which consists exclusively of the active principle.
- the grains of coated active principle are mixed cold with uncoated adjuvants.
- a powder consisting exclusively of adjuvant (s) can be used.
- the grains of coated adjuvants are mixed with the uncoated active ingredient.
- the mixture obtained is subjected to a compression step.
- the mixture obtained can be directly packaged in the form of sachets or capsules.
- a grain lubrication step To avoid adhesion of the coated grains obtained, whether it is in the case where all the grains are treated, or whether it is in the case where only a part of the grains is treated, there is interposed between the coating step and the pharmaceutical shaping step, a grain lubrication step.
- the granules or tablets obtained can be subjected to a ripening step. in an oven, for at least 8 hours, at a temperature between 45 and 60 ° C, preferably 55 ° C.
- an amount of matrix agent is used, representing by weight from 1 to 15% of the final composition, advantageously from 2 to 5%.
- an ester of behenic acid and alcohol is used as lipid matrix agent.
- the alcohol is chosen from the group comprising glycerol, polyglycerol, propylene glycol, propylene glycol combined with ethylene oxide and polyethylene glycol.
- These matrix agents have the advantage of having a melting point above 50 ° C., which prevents their disintegration at the compression temperature. In addition, this melting point is higher than the internal temperature of the human body (37 ° C), which allows the lipid agent to have a more marked matrix behavior.
- the spraying of a fatty acid and alcohol ester as a lipid matrix agent in addition to accelerating or slowing the release of the active principle, also masks the taste of the material.
- This is of real interest insofar as none of the current masking techniques makes it possible to mask the taste of the raw materials without excessively slowing down the release of the active principle.
- the ester of behenic acid and of glycerol having a melting point of between 69 and 74 ° C., therefore much higher than 50 ° C. is used.
- This ester results from the direct esterification of behenic acid on the glycerol to result in a mixture of glycerol mono-, di-, and tribhenenate.
- the lipid matrix agent is an ester of palmitostearic acid and alcohol.
- the adjuvant is chosen from hydrophobic diluents, hydrophilic diluents, binding agents, lubricants, alone or as a mixture.
- the hydrophobic diluting agent is dicalcium phosphate and the hydrophilic diluting agent is lactose.
- Dicalcium phosphate has the advantage of being very low in cost, which contributes to reducing the final cost of the composition. Furthermore, the use of lactose, as a hydrophilic diluting agent, makes it possible to adjust the hydrophilic / lipophilic balance necessary for the release of active principle.
- polyvinylpyrrolidone is used as binding agent, which makes it possible to reduce the compression forces of the pharmaceutical composition.
- the pharmaceutical composition comprises a lubricating agent chosen from the group comprising magnesium stearate and silicone talc, alone or in combination.
- the silicone talc is composed of 80% talc and 20% silicone oil.
- the invention also relates to the composition obtained by the method described above.
- this modified-release pharmaceutical composition can be obtained by other methods, and in particular that of wet granulation, in which water is used as the granulation solvent.
- Figure 1 is a representation as a function of time of the dissolution profile of batches of theophylline tablets prepared by the process of the invention.
- Figure 2 is a representation as a function of time of the dissolution profile of a batch of coated granules (2A, 2B) and tablets (2C) of acetylsalicylic acid produced according to the method of the invention.
- Figure 3 is a representation as a function of time of the dissolution profile of a batch of coated granules (3A) and tablets (3C) of paracetamol produced according to the method of the invention.
- FIG. 4 is a representation as a function of time of the dissolution profile of a pilot batch of ibuprofen tablets produced by wet granulation.
- FIG. 5 is a representation as a function of time of the dissolution profile of a batch of phenyl propanolamine and chlorpheniramine tablets produced by wet granulation.
- Figure 6 is a representation as a function of time of the dissolution profile of a batch of theophylline tablets produced by wet granulation.
- a mixture of 3 kg of powder comprising:
- hydrophobic diluting agent dicalcium phosphate dihydrate 90 g - binding agent: polyvmylpyrrolidone 90 g
- the lipid matrix agent (glycerol behenate marketed by the Applicant under the brand COMPRITOL® 880 ATO) is separately liquefied at 120 ° Celsius; - we spray on the heated powder mixture,
- Fluidization air flow (m 3 / h) 80 110 80 80
- the granules thus obtained are mixed in a mixer with a lubricant comprising 1% of magnesium stereate and 2% of silicone talc relative to the weight of the preparation, for 10 minutes.
- silicone talc a rate of 20% by weight of silicone oil is incorporated (fluid dimethicone 100 CST from DOW CORNING) in 80% talc by weight).
- Figure 1 there is shown the dissolution profile of batches of tablets obtained after a step of compressing the granules, according to the parameters of the preceding table, comprising 100 milligrams of theophylline.
- Curve 1 corresponds to lot 1.
- Curve 2 corresponds to lot 2.
- Curve 3 corresponds to lot 3.
- Curve 4 corresponds to lot 4.
- the spray air pressures are adjusted to values making it possible to promote the agglomeration of the grains (1.5 bar) then the formation of the homogeneous film of lipid matrix agent around the grains (2 bars ), and this continuously during the spraying step.
- the powder of acetylsalicylic acid is coated by spraying the lipid matrix agent on the individualized grains;
- FIG. 2 shows the profile of the dissolution in acid medium of the
- GATTAPRTNE compared to acetylsalycilique tablets coated with ethylcellulose and marketed by RHONE-POULENC under the brand "ROHDINE NC RP" ( Figure 2A).
- Dissolution tests are carried out according to the pharmacopoeia method (USP XXIII).
- the coated acetylsalycilic acid granules obtained are then mixed with a powder consisting of:
- the mixture obtained is then subjected to a compression step in order to obtain microencapsulated acetylsalycilic acid tablets.
- the tablets thus prepared have the advantage of being free of any organic solvent and the final product therefore presents no toxic risk.
- the method makes it possible to obtain products having good stability.
- the lipid matrix substance makes it possible to protect the active principle from any phenomenon of humidity during its storage, so that the hydrolysis of the active principle is extremely reduced.
- Example 3 In this example, the release profile of coated paracetamol for two different lipid matrix agents is compared. Example 2 is repeated, replacing acetylsalycilic acid with paracetamol. In addition, 9 g of COMPRITOL ® is used.
- the coated paracetamol granules obtained are then mixed with a powder made up in the same proportions, of microcrystalline cellulose, talc and magnesium stearate, then subjecting the mixture obtained for a compression step.
- compositions with release of active principle are prepared by a wet granulation process.
- One hundred grams (100 g) of granules are prepared comprising in mixture: - active principle: ibuprofen 60 g
- the granules are prepared by a wet granulation process in a granulator mixer comprising the following steps:
- the granules obtained are compressed with an alternative compression machine, well known for this application.
- FIG. 4 is a representation of the dissolution profile of a pilot batch produced according to the invention, of 300 mg ibuprofen tablets, at pH 6.8 (in vitro).
- the level of lipid matrix agent was determined to obtain a release profile of 90% of active principle in 12 hours.
- Curve 5 corresponds to a batch which has not been subjected to a ripening operation.
- Curve 6 corresponds to a batch having been subjected to a ripening operation in an oven for twenty-four hours at 55 ° C. It is found in this case that the dissolution rate is significantly lower over time and is stabilized.
- a mixture of one hundred grams (100 g) of powder is prepared containing:
- the level of lipid matrix is determined in order to obtain an active principle release profile close to the form sold under the registered trademark CONTAC® of the SMITHKLINE BEESHAM Laboratory.
- the granules are prepared by a wet granulation process in a granulator mixer comprising the following steps:
- the granule obtained is mixed with the dicalcium phosphate in a mixer for ten minutes. Then added to 97 g of granules thus obtained, 1.6 g of magnesium stearate and 1.4 g of a mixture of silicone talc similar to Example 1.
- the compression is carried out on an alternative compression press.
- Figure 5 is a representation of the dissolution profile of a batch of tablets produced according to the invention, comprising as active ingredient, 75 mg of phenylpropanolamine and 12 mg of chlorpheniramine.
- Curve 7 corresponds to a batch which has not been subjected to a ripening operation.
- Curve 8 corresponds to a batch having been subjected to a ripening operation in an oven for twenty-four hours at 55 ° C.
- Curve 9 corresponds to a batch of tablets marketed under the brand CONTACT ®. It is found that the dissolution profile of the pharmaceutical composition prepared according to the invention corresponds to that of CONTACT ®.
- the shape is stabilized over time by carrying out a ripening step.
- a mixture of 100 g of powder is prepared containing: - Theophylline: 33 g
- the level of lipid matrix agent is determined to obtain a release profile of 90% of active principle in 12 hours.
- the granules are prepared by a wet granulation process in a mixer-granulator comprising the following steps:
- the granules thus obtained are then mixed with 2 g of magnesium stearate, then compressed in a rotary compression press.
- Figure 6 is a representation of the dissolution profile of a batch of tablets, produced according to the invention comprising, as active ingredient, 100 mg of Theophylline.
- Curve 10 corresponds to a batch which has not been subjected to a ripening operation.
- Curve 1 1 corresponds to a batch having been subjected to a ripening operation in an oven for twenty-four hours at 55 ° C.
- the process for manufacturing the composition of the invention therefore has numerous advantages.
- this process is characterized by the low number of constituents that it implements as well as the low proportions of each of them.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Inorganic Chemistry (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR9612156 | 1996-10-01 | ||
FR9612156A FR2753904B1 (fr) | 1996-10-01 | 1996-10-01 | Composition pharmaceutique a liberation modifiee de principe actif, comportant une matrice, et procede de fabrication |
PCT/FR1997/001710 WO1998014176A1 (fr) | 1996-10-01 | 1997-09-29 | Procede de fabrication d'une composition pharmaceutique a liberation modifiee de principe actif, comportant une matrice |
Publications (2)
Publication Number | Publication Date |
---|---|
EP0935459A1 true EP0935459A1 (de) | 1999-08-18 |
EP0935459B1 EP0935459B1 (de) | 2002-06-12 |
Family
ID=9496393
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP97943017A Expired - Lifetime EP0935459B1 (de) | 1996-10-01 | 1997-09-29 | Verfahren zur herstellung einer pharmazeutischen zusammensetzung mit veränderter wirkstoffsfreisetzung, enthaltend eine matrix |
Country Status (9)
Country | Link |
---|---|
US (1) | US6194005B1 (de) |
EP (1) | EP0935459B1 (de) |
JP (1) | JP2001501218A (de) |
KR (1) | KR20000048761A (de) |
AU (1) | AU4464897A (de) |
DE (1) | DE69713367T2 (de) |
ES (1) | ES2176785T3 (de) |
FR (1) | FR2753904B1 (de) |
WO (1) | WO1998014176A1 (de) |
Families Citing this family (24)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2779651B1 (fr) * | 1998-06-16 | 2001-04-20 | Gattefosse Ets Sa | Procede pour la fabrication de comprimes a liberation prolongee de principe(s) actif(s) presentant une cinetique de dissolution d'ordre zero |
FR2784895B1 (fr) * | 1998-10-23 | 2004-12-17 | Gattefosse Ets Sa | Comprime a croquer a gout masque et liberation immediate du principe actif et procede de fabrication |
US10179130B2 (en) | 1999-10-29 | 2019-01-15 | Purdue Pharma L.P. | Controlled release hydrocodone formulations |
EP1623703B1 (de) | 1999-10-29 | 2011-10-05 | Euro-Celtique S.A. | Hydrocodon-Formulierungen mit gesteuerter Freisetzung |
SK285128B6 (sk) * | 1999-12-28 | 2006-07-07 | Zentiva, A. S. | Liečivý prípravok s riadeným uvoľňovaním obsahujúci tramadol hydrochlorid a spôsob jeho prípravy |
HU230686B1 (en) | 2000-10-30 | 2017-08-28 | Euro Celtique Sa | Controlled release hydrocodone compositions |
FR2822381B1 (fr) * | 2001-03-20 | 2004-10-22 | Bio Obtention Sc | Extrait de cucumis melo enrobe et/ou microencapsule dans un agent liposoluble a base de matiere grasse |
SK286107B6 (sk) * | 2002-04-12 | 2008-03-05 | Zentiva, A. S. | Analgeticky účinný perorálny liečivý prípravok s kontrolovaným uvoľňovaním opioidnej účinnej látky a spôsob jeho prípravy |
US20040043070A1 (en) * | 2002-05-14 | 2004-03-04 | Ayres James W. | Hot melt coating by direct blending and coated substrates |
US20030235613A1 (en) * | 2002-06-19 | 2003-12-25 | Cts Chemical Industries Ltd. | Popping oral administration form |
US20070141071A1 (en) * | 2003-05-14 | 2007-06-21 | Oregon State University | Hot melt coating by direct blending and coated substrates |
US7364755B2 (en) * | 2003-07-07 | 2008-04-29 | Synthon Ip Inc. | Modified calcium phosphate excipient |
US20080069891A1 (en) | 2006-09-15 | 2008-03-20 | Cima Labs, Inc. | Abuse resistant drug formulation |
US8445018B2 (en) | 2006-09-15 | 2013-05-21 | Cima Labs Inc. | Abuse resistant drug formulation |
EP1972336A1 (de) * | 2007-03-19 | 2008-09-24 | LEK Pharmaceuticals D.D. | Heißschmelz-Mikropellets |
DE102007026550A1 (de) | 2007-06-08 | 2008-12-11 | Bayer Healthcare Ag | Extrudate mit verbesserter Geschmacksmaskierung |
US20090004285A1 (en) * | 2007-06-29 | 2009-01-01 | Liangping Yu | Stable non-disintegrating dosage forms and method of making same |
FR2959130A1 (fr) * | 2010-04-21 | 2011-10-28 | Sanofi Aventis | Procede de preparation de compositions pharmaceutiques destinees a l'administration par voie orale comprenant un ou plusieurs principes actifs et les compositions les comprenant. |
WO2011143120A1 (en) | 2010-05-11 | 2011-11-17 | Cima Labs Inc. | Alcoholres i stant metoprolol - containing extended - release oral dosage forms |
US11071805B2 (en) | 2013-04-22 | 2021-07-27 | Sealantium Medical Ltd. | Fibrinogen-based tissue adhesive patches |
US11471556B2 (en) | 2015-10-19 | 2022-10-18 | Sealantium Medical Ltd. | Fibrinogen-based tissue adhesive patch |
CA3008674C (en) | 2015-10-19 | 2024-02-13 | Sealantium Medical Ltd | Improved fibrinogen-based tissue adhesive patch |
US20180207328A1 (en) * | 2017-01-22 | 2018-07-26 | Kamalesh K. Rao | Implantable Compositions for Pain Management |
CA3087126A1 (en) * | 2017-12-27 | 2019-07-04 | Graal S.R.L. | Process for the preparation of delayed release solid formulations |
Family Cites Families (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4129666A (en) | 1977-04-29 | 1978-12-12 | Walter Wizerkaniuk | Method of providing pellets with a water insoluble coating using a melt |
FR2573307B1 (fr) * | 1984-11-22 | 1988-06-10 | Virbac Ctre Rech Biolog | Implants anabolisants a liberation prolongee |
EP0421581A1 (de) | 1989-10-03 | 1991-04-10 | Warner-Lambert Company | Kaubare sprühgetrocknete spheroide Mikrokapseln, wachsüberzogene Mikrokapseln und Verfahren zu ihrer Herstellung |
DE4001622A1 (de) * | 1990-01-20 | 1991-07-25 | Thomae Gmbh Dr K | Orale arzneimittelformen von pimobendan |
JPH03232814A (ja) * | 1990-02-08 | 1991-10-16 | Shin Etsu Chem Co Ltd | 徐放性錠剤の製造方法 |
JP3078859B2 (ja) * | 1990-02-23 | 2000-08-21 | 武田薬品工業株式会社 | 安定な放出制御性製剤用コーティング剤 |
JP2553258B2 (ja) | 1991-05-20 | 1996-11-13 | 三菱化学株式会社 | ワックス被覆製剤の製造方法 |
GB9224855D0 (en) * | 1992-11-27 | 1993-01-13 | Smithkline Beecham Plc | Pharmaceutical compositions |
SE9301112D0 (sv) * | 1993-04-02 | 1993-04-02 | Orion-Yhtymae Oy | A new composition |
IL109770A0 (en) | 1993-05-29 | 1994-11-28 | Smithkline Beecham Corp | Thermal infusion process for preparing controlled release solid dosage forms of medicaments for oral administration and controlled release solid dosage forms of medicaments prepared thereby |
DK0744941T3 (da) * | 1994-02-16 | 2003-09-29 | Abbott Lab | Fremgangsmåde til fremstilling af findelte farmaceutiske formuleringer |
-
1996
- 1996-10-01 FR FR9612156A patent/FR2753904B1/fr not_active Expired - Lifetime
-
1997
- 1997-09-29 KR KR1019990702747A patent/KR20000048761A/ko active IP Right Grant
- 1997-09-29 ES ES97943017T patent/ES2176785T3/es not_active Expired - Lifetime
- 1997-09-29 EP EP97943017A patent/EP0935459B1/de not_active Expired - Lifetime
- 1997-09-29 AU AU44648/97A patent/AU4464897A/en not_active Abandoned
- 1997-09-29 JP JP10516277A patent/JP2001501218A/ja not_active Ceased
- 1997-09-29 US US09/269,468 patent/US6194005B1/en not_active Expired - Lifetime
- 1997-09-29 DE DE69713367T patent/DE69713367T2/de not_active Expired - Lifetime
- 1997-09-29 WO PCT/FR1997/001710 patent/WO1998014176A1/fr active IP Right Grant
Non-Patent Citations (1)
Title |
---|
See references of WO9814176A1 * |
Also Published As
Publication number | Publication date |
---|---|
FR2753904A1 (fr) | 1998-04-03 |
FR2753904B1 (fr) | 1998-10-30 |
WO1998014176A1 (fr) | 1998-04-09 |
AU4464897A (en) | 1998-04-24 |
ES2176785T3 (es) | 2002-12-01 |
EP0935459B1 (de) | 2002-06-12 |
KR20000048761A (ko) | 2000-07-25 |
US6194005B1 (en) | 2001-02-27 |
DE69713367D1 (de) | 2002-07-18 |
DE69713367T2 (de) | 2003-03-06 |
JP2001501218A (ja) | 2001-01-30 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
WO1998014176A1 (fr) | Procede de fabrication d'une composition pharmaceutique a liberation modifiee de principe actif, comportant une matrice | |
CA2483212C (fr) | Particules enrobees a liberation prolongee et comprimes les contenant | |
EP2435030B1 (de) | Schwebende pharmazeutische zusammensetzungen mit kontrollierter freisetzung | |
CA2493453C (fr) | Formulation pharmaceutique orale sous forme d'une pluralite de microcapsules permettant la liberation prolongee de principe(s) actif(s) peu soluble(s) | |
US6375987B1 (en) | Process for the manufacture of pharmaceutical composition with modified release of active principle comprising the matrix | |
EP0939626B1 (de) | Milnacipranhaltige darreichungsform mit verzögerter wirkstoffabgabe | |
EP2349227B1 (de) | Alkohol-resistentes Mikrogranulat | |
WO1999065471A1 (fr) | Procede pour la fabrication de comprimes a liberation prolongee de principe(s) actif(s) | |
CA2632547C (fr) | Composition a liberation prolongee de l'actif, son procede de preparation et son utilisation | |
WO1999026608A1 (fr) | Spheroides, procede de preparation et compositions pharmaceutiques | |
FR2881957A1 (fr) | Comprimes comprenant une substance biologiquement active et un excipient | |
EP1333812B1 (de) | Mikrogranulat auf wirkstoffbasis und verfahren zu seiner herstellung | |
EP1353663A1 (de) | Fenofibrattabletten | |
EP1549298B1 (de) | Sphäroide, deren herstellungsverfahren und sphäroidenhaltige arzneimittel | |
CA2437630A1 (fr) | Procede de fabrication d'un comprime flottant incluant de l'alfuzosine | |
FR2775597A1 (fr) | Pellet administrable par voie orale apte a ameliorer la biodisponibilite de la substance active, procede de fabrication | |
EP1123089A1 (de) | Geschmacksmaskierte kautablette mit sofortiger wirkstofffreisetzung sowie herstellungsverfahren | |
WO1992022305A1 (fr) | Composition therapeutique pour liberation prolongee de magnesium | |
EP0342106A1 (de) | Pillen mit wasserlöslichen Diltiazemsalzen mit programmierter Wirkstoffabgabe und Verfahren zur Herstellung | |
FR2742659A1 (fr) | Procede de fabrication de minispheres matricielles a liberation prolongee | |
WO2000025749A9 (fr) | Utilisation de gommes xanthanes pour la preparation de compositions pharmaceutiques | |
FR3020571A1 (fr) | Co-granules de gomme de xanthane et de gomme d'acacia |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
17P | Request for examination filed |
Effective date: 19990301 |
|
AK | Designated contracting states |
Kind code of ref document: A1 Designated state(s): BE CH DE ES FR GB IT LI |
|
17Q | First examination report despatched |
Effective date: 19990915 |
|
GRAG | Despatch of communication of intention to grant |
Free format text: ORIGINAL CODE: EPIDOS AGRA |
|
GRAG | Despatch of communication of intention to grant |
Free format text: ORIGINAL CODE: EPIDOS AGRA |
|
GRAH | Despatch of communication of intention to grant a patent |
Free format text: ORIGINAL CODE: EPIDOS IGRA |
|
GRAH | Despatch of communication of intention to grant a patent |
Free format text: ORIGINAL CODE: EPIDOS IGRA |
|
GRAA | (expected) grant |
Free format text: ORIGINAL CODE: 0009210 |
|
AK | Designated contracting states |
Kind code of ref document: B1 Designated state(s): BE CH DE ES FR GB IT LI |
|
REG | Reference to a national code |
Ref country code: GB Ref legal event code: FG4D Free format text: NOT ENGLISH |
|
REG | Reference to a national code |
Ref country code: CH Ref legal event code: EP |
|
RAP2 | Party data changed (patent owner data changed or rights of a patent transferred) |
Owner name: GATTEFOSSE HOLDING |
|
REF | Corresponds to: |
Ref document number: 69713367 Country of ref document: DE Date of ref document: 20020718 |
|
GBT | Gb: translation of ep patent filed (gb section 77(6)(a)/1977) |
Effective date: 20020801 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: LI Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20020930 Ref country code: CH Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20020930 |
|
REG | Reference to a national code |
Ref country code: ES Ref legal event code: FG2A Ref document number: 2176785 Country of ref document: ES Kind code of ref document: T3 |
|
PLBE | No opposition filed within time limit |
Free format text: ORIGINAL CODE: 0009261 |
|
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: NO OPPOSITION FILED WITHIN TIME LIMIT |
|
REG | Reference to a national code |
Ref country code: CH Ref legal event code: PL |
|
26N | No opposition filed |
Effective date: 20030313 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: BE Payment date: 20041014 Year of fee payment: 8 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: BE Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20050930 |
|
BERE | Be: lapsed |
Owner name: S.A. *GATTEFOSSE Effective date: 20050930 |
|
REG | Reference to a national code |
Ref country code: FR Ref legal event code: PLFP Year of fee payment: 19 |
|
REG | Reference to a national code |
Ref country code: FR Ref legal event code: PLFP Year of fee payment: 20 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: GB Payment date: 20160916 Year of fee payment: 20 Ref country code: DE Payment date: 20160914 Year of fee payment: 20 Ref country code: IT Payment date: 20160909 Year of fee payment: 20 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: FR Payment date: 20160928 Year of fee payment: 20 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: ES Payment date: 20160929 Year of fee payment: 20 |
|
REG | Reference to a national code |
Ref country code: DE Ref legal event code: R071 Ref document number: 69713367 Country of ref document: DE |
|
REG | Reference to a national code |
Ref country code: GB Ref legal event code: PE20 Expiry date: 20170928 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: GB Free format text: LAPSE BECAUSE OF EXPIRATION OF PROTECTION Effective date: 20170928 |
|
REG | Reference to a national code |
Ref country code: ES Ref legal event code: FD2A Effective date: 20180508 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: ES Free format text: LAPSE BECAUSE OF EXPIRATION OF PROTECTION Effective date: 20170930 |